Schisandra chinenesis (SC) has been reported to have ameliorative effect on osteoporosis. However, the mechanisms underlying the anti-osteoporosis activity of SC have not been clearly elucidated. In the present s...
https://ift.tt/2y6DZqn
Δευτέρα 1 Οκτωβρίου 2018
Inhibition of RANKL-stimulated osteoclast differentiation by Schisandra chinensis through down-regulation of NFATc1 and c-fos expression
Dietary supplement use among undergraduate male students in health and non-health cluster colleges of a public-sector university in Dammam, Saudi Arabia
Dietary supplements (DS) are nutraceuticals that improve overall health and well-being of an individual as well as reduce the risk of diseases. Evidence indicates a rising prevalence of these products worldwid...
https://ift.tt/2zLnqm2
Antidiabetic activity, glucose uptake stimulation and α-glucosidase inhibitory effect of Chrysophyllum cainito L. stem bark extract
Chrysophyllum cainito L., a tropical fruit tree, has been used as an alternative medicine for the treatment of diabetic patients in many countries. However, there is very limited scientific rationale for this med...
https://ift.tt/2y3eIgM
Protective effects and mechanisms of Terminalia catappa L. methenolic extract on hydrogen-peroxide-induced oxidative stress in human skin fibroblasts
Oxidative stress plays a crucial role in aging-related phenomenon, including skin aging and photoaging. This study investigated the protective role and possible mechanism of Terminalia catappa L. methanolic extra...
https://ift.tt/2zLoshJ
A Lanosteryl triterpene from Protorhus longifolia augments insulin signaling in type 1 diabetic rats
A substantial literature supports antidiabetic properties of the lanosteryl triterpene (methyl-3β-hydroxylanosta-9,24-dien-21-oate, RA-3) isolated from Protorhus longifolia stem bark. However, the molecular mecha...
https://ift.tt/2y6O9aB
Correction to: Medical Treatment Options for Patients with Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer Suffering from Brain Metastases and/or Leptomeningeal Disease
Enhanced digital features were retrospectively added to this article.
https://ift.tt/2zLItot
Environmental dimensions of antibiotic resistance: Assessment of basic science gaps
Abstract
Antibiotic resistance is one of the major problems facing medical practice in the 21st century. Historical approaches to managing antibiotic resistance have often focused on individual patients, specific pathogens, and particular resistance phenotypes. However, it is increasingly recognized that antibiotic resistance is a complex ecological and evolutionary problem. As such, understanding the dynamics of antibiotic resistance requires integration of data on the diverse mobile genetic elements often associated to antibiotic resistance genes, and their dissemination through various mechanisms of horizontal gene transfer between bacterial cells and environments. Most important is understanding of the fate and effects of antibiotics at sub-inhibitory concentration and co-selection. This opinion paper identifies key knowledge gaps in our understanding of resistance phenomena, and outlines research needs that should be addressed to help us manage resistance into the future.https://ift.tt/2OtQw1l
Non-orthogonal one-step calibration method for robotized transcranial magnetic stimulation
Robotized transcranial magnetic stimulation (TMS) combines the benefits of neuro-navigation with automation and provides a precision brain stimulation method. Since the coil will normally remain unmounted betw...
https://ift.tt/2xULhhw
Combining multi-scale composite windows with hierarchical smoothing strategy for fingerprint orientation field computation
Orientation field (OF) plays a very significant role in automatic fingerprint recognition systems. Many algorithms have been proposed for the estimation of fingerprints' OF but it is hard to solve the dilemma ...
https://ift.tt/2NgYDcV
Blisters Induced by PUVA: A Report of 5 Cases
Measurement of the Psychological Impact of Psoriasis on Patients Receiving Systemic Treatment
Epidermal Nevi and Related Syndromes — Part 1: Keratinocytic Nevi
Epidermal Nevi and Related Syndromes —Part 2: Nevi Derived from Adnexal Structures
The Library of the Spanish Academy of Dermatology and Venereology (AEDV)
Functional Surgery for Malignant Subungual Tumors: A Case Series and Literature Review
Systemic Treatment of Moderate to Severe Psoriasis in Pediatric Patients in Galicia, Spain: A Descriptive Study
A. Batalla, R. Fernández-Torres, L. Rodríguez-Pazos, B. Monteagudo, R. Pardavila-Riveiro, R. Rodríguez-Lojo, Á. Zulaica, M. Cabanillas, E. Fonseca, Á. León, L. Fernández-Díaz, T. Abalde, L. Salgado-Boquete, F. Valdés, M.J. Seoane-Pose, H. Vázquez-Veiga, I. Suárez-Conde, J. Álvarez-López, Á. Flórez
Actas Dermosifiliogr.2018;109:722-32
Abstract - Full Text - PDF
https://ift.tt/2NXg879
Diffuse Erythema and Acral Hyperkeratosis in a Newborn
Multiple Acquired Hypopigmented Nodules on the Anterior Chest
Panniculitis Due to Atypical Mycobacteria After Mesotherapy
Inflammation of Actinic Keratosis During Panitumumab Therapy
Hematopoietic Stem Cell Transplantation in the Era of Engineered Cell Therapy
Abstract
Purpose of Review
Cellular therapy using T cells modified to express chimeric antigen receptors (CAR-T cells) has had striking success in patients that have failed previous treatment for CD19+ B cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or acute lymphoblastic leukemia (ALL). Curative therapy for this group of diseases has previously been limited to allogeneic hematopoietic cell transplantation HCT (alloHCT). The recent results of CAR-T cell therapy raise the question of how best to integrate CAR-T cell therapy and alloHCT in the care of these patients.
Recent Findings
Within the past 2 years, results from larger trials and increased follow-up of patients treated with CD19 CAR-T cell therapy suggest that some may achieve durable remission without transplant.
Summary
The balance of efficacy and toxicity for CAR-T cell therapy and alloHCT vary by disease type, disease status at the time of treatment, patient characteristics, and the specific therapy employed. There are early signals that subsequent transplantation of patients who have achieved remission with CAR-T may be a potentially viable (though expensive) strategy.
https://ift.tt/2RhHiUg
Bispecific Antibodies for the Treatment of Acute Myeloid Leukemia
Abstract
Purpose of review
Bispecific antibodies combine antigen recognition sites from two or more antibodies into a single construct allowing simultaneous binding to multiple targets. Bispecific antibodies exist which can redirect immune effector cells against acute myeloid leukemia (AML) targets. This review will highlight the progress to date and the challenges in developing bispecific antibodies for the treatment of AML.
Recent findings
Currently, a number of bispecific antibody formats including bispecific T cell engagers, dual affinity retargeting proteins, and tandem diabodies are in clinical development for AML. These antibodies target antigens present on AML blasts, including CD33, and the low affinity IL3 receptor, CD123. T cell redirecting bispecific antibodies in early phase clinical trials for AML include AG330, flotetuzumab, JNJ-63709178, and AMV564.
Summary
Bispecific antibodies represent a promising immunotherapeutic approach for the treatment of cancer. The results of ongoing studies in AML will elucidate the potential for these agents in AML.
https://ift.tt/2y4H8qz
Correction to: Retraction of: Tumor Protein D52-Like 2 Contributes to Proliferation of Breast Cancer Cells; 10.10.89/cbr.2014.1723 Cancer Biother Radiopharm 2017;32(10):387. DOI: 10.1089/cbr.2014.1723.retract
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2Iv1IW1
Correction to: Retraction of: Tumor Protein D52-Like 2 Accelerates Gastric Cancer Cell Proliferation; 10.10.89/cbr.2014.1766 Cancer Biother Radiopharm 2017;32(10):388. DOI: 10.1089/cbr.2014.1766.retract
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2OpL7bC
Characterization of Genetic and Epigenetic Variation in Sperm and Red Blood Cells from Adult Hatchery and Natural-Origin Steelhead, Oncorhynchus mykiss
While the goal of most conservation hatchery programs is to produce fish that are genetically and phenotypically indistinguishable from the wild stocks they aim to restore, there is considerable evidence that salmon and steelhead reared in hatcheries differ from wild fish in phenotypic traits related to fitness. Some evidence suggests that these phenotypic differences have a genetic basis (e.g. domestication selection) but another likely mechanism that remains largely unexplored is that differences between hatchery and wild populations arise as a result of environmentally-induced heritable epigenetic change. As a first step toward understanding the potential contribution of these two possible mechanisms, we describe genetic and epigenetic variation in hatchery and natural-origin adult steelhead, Oncorhynchus mykiss, from the Methow River, WA. Our main objectives were to determine if hatchery and natural-origin fish could be distinguished genetically and whether differences in epigenetic programming (DNA methylation) in somatic and germ cells could be detected between the two groups. Genetic analysis of 72 fish using 936 SNPs generated by Restriction Site Associated DNA Sequencing (RAD-Seq) did not reveal differentiation between hatchery and natural-origin fish at a population level. We performed Reduced Representation Bisulfite Sequencing (RRBS) on a subset of 10 hatchery and 10 natural-origin fish and report the first genome-wide characterization of somatic (red blood cells (RBCs)) and germ line (sperm) derived DNA methylomes in a salmonid, from which we identified considerable tissue-specific methylation. We identified 85 differentially methylated regions (DMRs) in RBCs and 108 DMRs in sperm in steelhead reared for their first year in a hatchery environment compared to those reared in the wild. This work provides support that epigenetic mechanisms may serve as a link between hatchery rearing and adult phenotype in steelhead; furthermore, DMRs identified in germ cells (sperm) highlight the potential for these changes to be passed on to future generations.
https://ift.tt/2NWRq7b
The Role of Standing Variation in the Evolution of Weediness Traits in South Asian Weedy Rice (Oryza spp.)
Weedy rice (Oryza spp.) is a problematic weed of cultivated rice (O. sativa) around the world. Recent studies have established multiple independent evolutionary origins of weedy rice, raising questions about the traits and genes that are essential for the evolution of this weed. Among world regions, South Asia stands out due to the heterogeneity of its weedy rice populations, which can be traced to at least three origins: two through de-domestication from distinct cultivated rice varieties, and one from local wild rice (O. rufipogon/O. nivara). Here we examine five traits considered typical of or advantageous to weedy rice in weedy, cultivated and wild rice samples from South Asia. We establish that convergence among all three weed groups occurs for easy seed shattering, red pericarp color, and compact plant architecture, suggesting that these traits are essential for weed success in the South Asian agricultural environment. A high degree of convergence for black hull color is also seen among weeds with wild ancestors and weeds evolved from the aus cultivated rice group. We also examine polymorphism in five known domestication candidate genes, and find that Rc and Bh4 are associated with weed seed pericarp color and hull color, respectively, and weedy alleles segregate in the ancestral populations, as do alleles for the seed dormancy-linked gene Sdr4. The presence of a domestication related allele at the seed shattering locus, sh4, in weedy rice populations with cultivated ancestry supports a de-domestication origin for these weedy groups, and raises questions about the reacquisition of the shattering trait in these weedy populations. Our characterization of weedy rice phenotypes in South Asia and their associated candidate genes contribute to the emerging understanding of the mechanisms by which weedy rice evolves worldwide, suggesting that standing ancestral variation is often the source of weedy traits in independently evolved groups, and highlighting the reservoir of genetic variation that is present in cultivated varieties as well as in wild rice, and its potential for phenotypic evolution.
https://ift.tt/2NeTphW
Emergence of Klebsiella pneumoniae harboring the aac(6')-Ian amikacin resistance gene [Letters]
Carbapenemase-producing Enterobacteriaceae (CPE) have become a major public health concern worldwide (1)....
https://ift.tt/2DKGFju
Pentoxifylline alone or in combination with gentamicin or vancomycin inhibits live microbe-induced pro-inflammatory cytokine production in human cord blood and cord blood monocytes in vitro [Biologic Response Modifiers]
Introduction: Neonatal sepsis and its accompanying inflammatory response contribute to substantial morbidity and mortality. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses transcription and production of pro-inflammatory cytokines, is a candidate adjunctive therapy for newborn sepsis. We hypothesized that PTX decreases live microbe-induced inflammatory cytokine production in newborn blood.
Methods: Cord blood was stimulated with live microorganisms commonly encountered in newborn sepsis (Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, or Candida albicans), and simultaneously treated with antimicrobial agents (gentamicin, vancomycin, or amphotericin B) and/or clinically relevant concentrations of PTX. Microbial colony counts were enumerated by plating, supernatant cytokines measured by multiplex assay, intracellular cytokines and signaling molecules by flow cytometry, and mRNA by qRT PCR.
Results: PTX inhibited concentration-dependent E. coli-, S. aureus-, S. epidermidis-, and C. albicans-induced TNF and E. coli-induced IL-1β production in whole blood, with greater suppression of pro-inflammatory cytokines in combination with antimicrobial agents. Likewise, PTX suppressed E. coli-induced monocytic TNF and IL-1β, whereby combined PTX and gentamicin led to significantly greater reduction of TNF and IL-1β. The anti-inflammatory effect of PTX on microbe-induced pro-inflammatory cytokine production was accompanied by inhibition of TNF mRNA expression, and was achieved without suppressing the production of the anti-inflammatory IL-10. Of note, microbial colony counts in newborn blood were not increased by PTX.
Conclusion: Our findings demonstrated that PTX inhibited microbe-induced pro-inflammatory cytokine production, especially when combined with antimicrobial agents, without enhancing microbial proliferation in human cord blood in vitro, thus supporting its utility as candidate adjunctive agent for newborn sepsis.
https://ift.tt/2DOgV5Y
Antimicrobial susceptibility of 260 Clostridium botulinum types A, B, Ba and Bf strains and a neurotoxigenic Clostridium baratii type F strain isolated from California infant botulism patients [Susceptibility]
Infant botulism is an infectious intestinal toxemia that results from colonization of the infant large bowel by Clostridium botulinum (or rarely, by neurotoxigenic C. baratii or C. butyricum), with subsequent intraintestinal production and absorption of botulinum neurotoxin that then produces flaccid paralysis. The disease is often initially misdiagnosed as suspected sepsis or meningitis, diagnoses that require prompt empiric antimicrobial therapy. Antibiotics may also be needed to treat infectious complications of infant botulism, such as pneumonia or urinary tract infection. Clinical evidence suggests (see included case report) that broad-spectrum antibiotics that are eliminated by biliary excretion may cause progression of the patient's paralysis by lysing C. botulinum vegetative cells in the large bowel lumen and thereby increasing the amount of botulinum neurotoxin available for absorption. The purpose of this antimicrobial susceptibility study was to identify an antimicrobial agent with little or no activity against C. botulinum that could be used to treat infant botulism patients initially diagnosed with suspected sepsis or meningitis, or who acquired secondary infections, without lysing C. botulinum. Testing of 12 antimicrobial agents indicated that almost all California infant botulism patient isolates are susceptible to most clinically utilized antibiotics and are also susceptible to newer antibiotics not previously tested against large numbers of C. botulinum patient isolates. No antibiotic with little or no activity against C. botulinum was identified. These findings reinforce the importance of promptly treating infant botulism patients with Human Botulism Immune Globulin (BIG-IV; BabyBIG®).
https://ift.tt/2xSrbEN
A simple alternative sampling method for benznidazole pharmacokinetic assessment: a dried blood spot technique-based LC-MS/MS method [Analytical Procedures]
Chagas Disease (CD) is recognized as one of the major global neglected tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ has been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-PD relationships in CD. The purpose this study was to develop and validate a bioanalytical method to quantify BNZ levels in small volume whole blood samples collected as dried blood spots (DBS). The analysis was performed using high performance liquid chromatography positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng.mL–1. Intra- and inter-day precisions and biases were less than 14.87% (n = 9) and 9.81% (n = 27), respectively. The recovery rates ranged from 94 to 100% and no matrix effect. There was no haematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 = 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for over one year. This article describes the first micro-sampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and paediatric patients in remote endemic areas and help to address existing knowledge gaps in the treatment in CD.
https://ift.tt/2DUIPgm
A Phase 1 Study to Assess the Pharmacokinetics of Intravenous Plazomicin in Adult Subjects with Varying Degrees of Renal Function [Clinical Therapeutics]
Plazomicin is an FDA-approved aminoglycoside for the treatment of complicated urinary tract infection. In this open-label study, 24 adults with normal renal function or mild, moderate, or severe renal impairment (n = 6 per group) received a single dose of plazomicin 7.5 mg/kg as a 30-min intravenous infusion. Total clearance declined with renal impairment, resulting in 1.98-fold and 4.42-fold higher plazomicin AUC0– values in subjects with moderate and severe impairment, respectively, relative to normal renal function.
https://ift.tt/2xSrb7L
Tenofovir exposure during pregnancy and postpartum in women receiving tenofovir disoproxil fumarate for the prevention of mother-to-child transmission of hepatitis B virus [Pharmacology]
We assessed tenofovir exposure during pregnancy and postpartum in hepatitis B virus (HBV)-infected, HIV-uninfected, women receiving tenofovir disoproxil fumarate (TDF) to prevent mother-to-child transmission of HBV. Data from 154 women who received TDF within a randomized-controlled trial were included. Individual plasma tenofovir exposures (AUC0-24) were estimated using a population pharmacokinetic approach. Estimated geometric mean tenofovir AUC0-24 was 20% (95% CI: 19-21%) lower during pregnancy compared to postpartum; this modest reduction in the absence of HBV transmission suggests no dose adjustment is needed.
https://ift.tt/2DUID0C
Tri-chlorination of a teicoplanin type glycopeptide antibiotic by the halogenase StaI evades resistance [Mechanisms of Resistance]
Glycopeptide antibiotics (GPAs) include clinically important drugs used for the treatment of infections caused by Gram positive pathogens. These antibiotics are specialized metabolites produced by several genera of actinomycetes bacteria. While many GPAs are highly chemically modified, A47934 is a relatively unadorned GPA lacking sugar or acyl modifications, common to other members of the class, but which is chlorinated at three distinct sites. The biosynthesis of A47934 is encoded by a 68 kb gene cluster in Streptomyces toyocaensis NRRL 15009. The cluster includes all the necessary genes for the synthesis of A47934 including two predicted halogenase genes, staI and staK. In this study, we report that only one of the halogenase genes, staI, is necessary and essential for A47934 biosynthesis. Chlorination of the A47934 scaffold is important for antibiotic activity as assessed by binding affinity for the target N-acyl-D-Ala-D-Ala. Surprisingly, chlorination is also vital to avoid activation of enterococcal and Streptomyces VanB-type GPA resistance through induction of resistance genes. Phenotypic assays showed stronger induction of GPA resistance by the dechlorinated compared to the chlorinated GPA. Correspondingly, the relative expression of enterococcal vanA resistance gene was shown to be increased by the dechlorinated compared to the chlorinated compound. These results provide insight into the biosynthesis of GPAs and the biological function of GPA chlorination for this medically important class of antibiotic.
https://ift.tt/2xSflKE
A high rate of ceftobiprole resistance among clinical MRSA from a hospital in central Italy [Mechanisms of Resistance]
Ceftobiprole is a fifth-generation cephalosporin with activity against MRSA. One-year surveillance at the Regional Hospital of Ancona (Italy) disclosed a 12% ceftobiprole resistance rate (12/102 isolates, MIC ≥4 mg/L). Epidemiological characterization demonstrated that the resistant isolates all belonged to different clones. PBP analysis showed substitutions in all PBPs and a novel insertion in PBP2a. Genes mecB and mecC were not detected. Ceftobiprole susceptibility screening is essential to avoid therapeutic failure and spread of ceftobiprole-resistant strains.
https://ift.tt/2DO1iLH
Pharmacokinetics of Intravenous Isavuconazole in Solid Organ Transplant Recipients [Clinical Therapeutics]
Isavuconazole may be useful in treating and preventing fungal infections in solid organ transplant (SOT) recipients due to its safety profile and activity against Aspergillus and some Mucorales. Isavuconazole has favourable pharmacokinetics based on clinical trials in various patient populations, but data are limited in SOT recipients. We evaluated the steady state pharmacokinetics of Isavuconazole in 26 SOT recipients receiving the drug intravenously for prophylaxis. There was moderate inter-patient variability in isavuconazole pharmacokinetic parameters (coefficients of variation of 51% for area under the plasma concentration-time curve (AUC) and 59% for trough plasma concentration), which were in general less than previously reported for other mould-active azoles such as voriconazole and posaconazole. AUC and steady state trough plasma concentrations (Ctrough) were significantly lower in women, patients with body mass index ≥18.5 kg/m2, and those receiving hemodialysis. Trough plasma concentrations were highly-correlated with AUCs (R2=0.94), and can serve as suitable measure of isavuconazole exposure in patients. In conclusion, moderate inter-patient variability in isavuconazole exposure, identification of factors associated with lower exposure, recognition that Ctrough is a surrogate marker for AUC and availability of a simple analytical method, suggest that therapeutic drug monitoring (TDM) may be useful for guiding treatment in at least some SOT recipients. Future studies are needed to correlate isavuconazole exposure with patients' clinical outcomes, and to determine the clinical role of TDM.
https://ift.tt/2xUyprI
Nitazoxanide: A Therapeutic Option for Adenovirus Related Enteritis in Immunocompromised Adults [Letters]
Clinical efficacy of cidofovir for treatment of adenovirus-related disease is limited and toxicity is a major concern....
https://ift.tt/2DUI4Uy
Correlation of invitro susceptibility based on MICs and SQLE mutations with clinical response to terbinafine in patients with tinea corporis/cruris [Clinical Therapeutics]
Recalcitrant dermatophytoses are on the rise in India. High MICs of terbinafine (TRB) and squalene epoxidase (SQLE) mutations conferring resistance in Trichophyton spp have been recently documented. However, studies correlating laboratory data with clinical response to TRB in tinea corporis/cruris are lacking. This study investigated the clinico-mycological profile of 85 tinea corporis/cruris patients, and performed antifungal susceptibility testing by CLSI micro-broth dilution and SQLE mutation analysis of isolates obtained and correlated these with the response to TRB. Cases confirmed by KOH mount of skin scrapings were started on TRB 250 mg once a day (OD). If >50% clinical clearance was achieved by 3 weeks, the same dose was continued (Group 1). If response was <50%, the dose was increased to 250 mg twice a day (BD) (Group 2). If the response still remained below 50% after 3 weeks of BD, the patients were treated with itraconazole (ITR; Group 3). Overall, 64 patients' (75.3%) skin scrapings yielded growth on culture. Strikingly all isolates were confirmed as Trichophyton interdigitale by ITS sequencing. Thirty-nine (61%) isolates had TRB MICs ≥1 µg/ml. Complete follow-up data was available for 30 culture positive patients. A highly significant difference in modal MICs to TRB among the three treatment response groups was noted (p=0.009).Interestingly, 8 of the 9 patients in group 3 harboured isolates exhibiting elevated TRB MICs (8-32µg/ml) and SQLE mutations. The odds of achieving cure with TRB MIC<1 µg/ml strains were 2.5 times the odds of achieving cure with the strain exhibiting MIC ≥1 µg/ml.
https://ift.tt/2xQsDav
Selective inhibition of Neisseria gonorrhoeae by a dithiazoline in mixed infections with Lactobacillus gasseri [Experimental Therapeutics]
The Gram-negative human pathogen Neisseria gonorrhoeae has progressively developed resistance to antibiotic monotherapies, and recent failures of dual-drug therapy have heightened concerns that strains resistant to all available antibiotics will begin circulating globally. Targeting bacterial cell wall assembly has historically been effective at treating infections with N. gonorrhoeae, but as the effectiveness of β-lactams (including cephalosporins) are challenged by increasing resistance, research has expanded into compounds that target the numerous other enzymes with roles in peptidoglycan metabolism. One example is the dithiazoline compound JNJ-853346 (DTZ), which inhibits the activity of an E. coli serine protease L,D-carboxypeptidase (LdcA). Recently, the characterization of an LdcA homolog in N. gonorrhoeae revealed localization and activity differences from the characterized E. coli LdcA, prompting us to explore the effectiveness of DTZ against N. gonorrhoeae. We found that DTZ is effective at inhibiting N. gonorrhoeae in all growth phases, unlike the specific stationary-phase inhibition seen in E. coli. Surprisingly, DTZ does not inhibit gonococcal LdcA enzyme activity, nor is DTZ sensitivity significantly decreased in ldcA mutants. While effective against numerous N. gonorrhoeae strains, including recent multi-drug resistant isolates, DTZ is much less effective at inhibiting growth of the commensal species Lactobacillus gasseri. DTZ treatment during co-infections of epithelial cells resulted in significant lowering of gonococcal burden and IL-8 secretion without significantly impacting recovery of viable L. gasseri. This selective toxicity presents a possible pathway for the use of DTZ as an effective anti-gonococcal agent at concentrations that do not impact vaginal commensals.
https://ift.tt/2DUHR3I
Emergence and within-host genetic evolution of methicillin-resistant Staphylococcus aureus resistant to linezolid in a cystic fibrosis patient [Mechanisms of Resistance]
Methicillin resistant Staphylococcus aureus (MRSA) infection has increased in recent years among cystic fibrosis (CF) patients. Linezolid (LZD) is one of the anti staphylococci antibiotic widely used in this context. Although LZD resistance is rare, it has been described as often associated with long term treatments. Thirteen MRSA strains isolated over 5 years from one CF patient were studied for LZD resistance emergence and underwent whole genome sequencing (WGS). Resistance emerged after three 15 day LZD therapeutic regimens over 4 months. It was associated with the G2576T mutation in all the 5 rrl copies along with a very high MIC (>256mg/L) and a strong increase of the generation time. Resistant strains isolated during the ensuing LZD therapeutic regimens and until 13 months after LZD stopped, harbored only 3 or 4 rrl mutated copies, associated with lower MICs (8 to 32mg/L) and low to moderate generation time increase. Despite these differences, whole genome sequencing allowed us to determine that all isolates, including the susceptible one isolated before LZD treatment, belonged to the same lineage. In conclusion, LZD resistance can emerge rapidly in CF patients and persist without linezolid selective pressure in MRSA colonizing strains belonging to the same lineage.
https://ift.tt/2xOcNxe
A review of the diversity in taxonomy, definitions, scope, and roles in forensic medicine: implications for evidence-based practice
Abstract
The scope, roles, and tasks of forensic medicine and forensic medical experts currently vary widely between countries and legal systems, which has resulted in barriers to organization, standard setting, and quality assurance for practice in forensic medicine, including for reporting. The legal fact finder is thus confronted with variability in the quality, structure, and content of forensic medical reports. We sought to define and categorize the scope, methods, and practices that fall under the description of forensic medicine, the various issues encountered in current forensic medical practice, and the potential role of evidence-based practice in forensic medicine. We searched electronic databases and reviewed relevant articles, as well as conducting personal correspondences with forensic medical practitioners around the world, to obtain a description of current forensic medical practice. The terms forensic medicine, legal medicine, medical jurisprudence, medico-legal services, forensic pathology, and clinical forensic medicine are used with mixed interpretations in different countries. The systems and services rendered are not uniform either. The methods used by forensic medical practitioners are not always evidence-based, or based on standardized methods, and vary greatly between experts and centers. There are also no universally accepted guidelines to prepare a standard and admissible report. The lack of a uniform system in forensic medicine creates difficulties in assessing the development and performance of forensic medicine as a distinct discipline. To prepare evidence-based forensic medical reports, generally accepted guidelines are necessary.
https://ift.tt/2Nh3OJJ
Feasibility of multi-parametric PET and MRI for prediction of tumour recurrence in patients with glioblastoma
Abstract
Background
Recurrence in glioblastoma patients often occur close to the original tumour and indicates that the current treatment is inadequate for local tumour control. In this study, we explored the feasibility of using multi-modality imaging at the time of radiotherapy planning. Specifically, we aimed to identify parameters from pre-treatment PET and MRI with potential to predict tumour recurrence.
Materials and methods
Sixteen patients were prospectively recruited and treated according to established guidelines. Multi-parametric imaging with 18F-FET PET/CT and 18F-FDG PET/MR including diffusion and dynamic contrast enhanced perfusion MRI were performed before radiotherapy. Correlations between imaging parameters were calculated. Imaging was related to the voxel-wise outcome at the time of tumour recurrence. Within the radiotherapy target, median differences of imaging parameters in recurring and non-recurring voxels were calculated for contrast-enhancing lesion (CEL), non-enhancing lesion (NEL), and normal appearing grey and white matter. Logistic regression models were created to predict the patient-specific probability of recurrence. The most important parameters were identified using standardized model coefficients.
Results
Significant median differences between recurring and non-recurring voxels were observed for FDG, FET, fractional anisotropy, mean diffusivity, mean transit time, extra-vascular, extra-cellular blood volume and permeability derived from scans prior to chemo-radiotherapy. Tissue-specific patterns of voxel-wise correlations were observed. The most pronounced correlations were observed for 18F-FDG- and 18F-FET-uptake in CEL and NEL. Voxel-wise modelling of recurrence probability resulted in area under the receiver operating characteristic curve of 0.77 from scans prior to therapy. Overall, FET proved to be the most important parameter for recurrence prediction.
Conclusion
Multi-parametric imaging before radiotherapy is feasible and significant differences in imaging parameters between recurring and non-recurring voxels were observed. Combining parameters in a logistic regression model enabled patient-specific maps of recurrence probability, where 18F-FET proved to be most important. This strategy could enable risk-adapted radiotherapy planning.
https://ift.tt/2P1jdj6
The 3PAs: An Update on the Association of Pheochromocytomas, Paragangliomas, and Pituitary Tumors
Horm Metab Res
DOI: 10.1055/a-0661-0341
Pituitary adenomas (PA) and pheochromocytomas/paragangliomas (PHEO/PGL) are rare tumors. Although they may co-exist by coincidence, there is mounting evidence that genes predisposing in PHEO/PGL development, may play a role in pituitary tumorigenesis. In 2012, we described a GH-secreting PA caused by an SDHD mutation in a patient with familial PGLs and found loss of heterozygosity at the SDHD locus in the pituitary tumor, along with increased hypoxia-inducible factor 1α (HIF-1α) levels. Additional patients with PAs and SDHx defects have since been reported. Overall, prevalence of SDHx mutations in PA is very rare (0.3–1.8% in unselected cases) but we and others have identified several cases of PAs with PHEOs/PGLs, like our original report, a condition which we termed the 3 P association (3PAs). Interestingly, when 3PAs is found in the sporadic setting, no SDHx defects were identified, whereas in familial PGLs, SDHx mutations were identified in 62.5–75% of the reported cases. Hence, pituitary surveillance is recommended among patients with SDHx defects. It is possible that the SDHx germline mutation-negative 3PAs cases may be due to another gene, epigenetic changes, mutations in modifier genes, mosaicism, somatic mutations, pituitary hyperplasia due to ectopic hypothalamic hormone secretion or a coincidence. PA in 3PAs are mainly macroadenomas, more aggressive, more resistant to somatostatin analogues, and often require surgery. Using the Sdhb +/− mouse model, we showed that hyperplasia may be the first abnormality in tumorigenesis as initial response to pseudohypoxia. We also propose surveillance and follow-up approach of patients presenting with this association.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2OYHFlc
Double trouble: visceral leishmaniasis in twins after traveling to Tuscany – a case report
Leishmaniasis is endemic in many countries worldwide, with a prevalence of 12 million people infected, and an estimated annual incidence of 500 000 visceral leishmaniasis cases. In Europe visceral leishmaniasi...
https://ift.tt/2NZF6TF
Modeling tuberculosis dynamics with the presence of hyper-susceptible individuals for Ho Chi Minh City from 1996 to 2015
The depletion of CD4 cell is the underlying reason for TB hyper-susceptibility among people with HIV. Consequently, the trend of TB dynamics is usually hidden by the HIV outbreak.
https://ift.tt/2Ng4uit
Copenhagen Prospective Personalized Oncology (CoPPO) - Clinical utility of using molecular profiling to select patients to phase 1 trials.
Purpose: We evaluated the clinical benefit of tumor molecular profiling (MP) to select treatment in the phase 1 setting. Experimental Design: Patients with advanced solid cancers and exhausted treatment options referred to a phase 1 unit were included in a prospective single-centre single-arm open-label study (NCT02290522). Tumor biopsies were obtained for comprehensive genomic analysis including whole exome sequencing (WES) and RNA sequencing. When possible, patients were treated with regimen matched to the genomic profile. Primary endpoint was progression free survival. Results: From May 2013 to January 2017 a total of 591 patients were enrolled with 500 patients undergoing biopsy. Genomic profiles were obtained in 460 patients and a potential actionable target was identified in 352 (70%) of 500 biopsied patients. One hundred and one patients (20%) received matched treatment based on either gene mutations or RNA expression levels of targets available in early clinical trials or off-label treatment. Objective response according to RECIST1.1 was observed in 15/101 patients (0% CR, 15% PR) with a median PFS of 12 weeks (95% CI 9.9-14.4). Conclusions: Our study supports the feasibility of genomic profiling to select patients in the phase 1 setting and suggests that genomic matching can be beneficial for a minor subset of patients with no other treatment options. Randomized studies may validate this assumption.
https://ift.tt/2zLk6Ht
Targeting resistance against the MDM2 inhibitor RG7388 in glioblastoma cells by the MEK inhibitor trametinib
Purpose: Resistance is an obstacle of glioma therapy. Despite targeted interventions, tumors harbor primary resistance or become resistant over short course of treatment. This study examined the mouse double minute 2 (MDM2) inhibitor RG7388 together with radiotherapy and analyzed strategies to overcome acquired MDM2 inhibitor resistance in glioblastoma. Experimental Design: Effects of RG7388 and radiotherapy were analyzed in p53 wild-type glioblastoma cell lines and glioma-initiating cells. RG7388 resistant cells were generated by increasing RG7388 doses over three months. Regulated pathways were investigated by microarray, qRT-PCR and immunoblot analysis and specifically inhibited to evaluate rational salvage therapies at RG7388 resistance. Effects of RG7388 and trametinib treatment were challenged in an orthotopical mouse model with RG7388 resistant U87MG glioblastoma cells. Results: MDM2 inhibition required functional p53 and showed synergistic activity with radiotherapy in first-line treatment. Long-term exposure to RG7388 induced resistance by activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) - insulin growth factor binding protein 1 (IGFBP1) signaling cascade, which was specifically overcome by ERK1/2 pathway inhibition with trametinib and knockdown of IGFBP1. Combining trametinib with continued RG7388 treatment enhanced anti-tumor effects at RG7388 resistance in vitro and in vivo. Conclusions: These data provide a rationale for combining RG7388 and radiotherapy as first-line therapy with a specific relevance for tumors insensitive to alkylating standard chemotherapy and for the addition of trametinib to continued RG7388 treatment as salvage therapy after acquired resistance against RG7388 for clinical practice.
https://ift.tt/2zLk7ev
The Role of Angiogenesis in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers and is the second leading cause of cancer-related deaths worldwide. The hypervascular nature of most HCC tumors underlines the importance of angiogenesis in the pathobiology of these tumors. Several angiogenic pathways have been identified as being dysregulated in HCC, suggesting they may be involved in the development and pathogenesis of HCC. These data provide practical targets for systemic treatments such as those targeting the vascular endothelial growth factor receptor and its ligand. However, the clinical relevance of other more recently identified angiogenic pathways in HCC pathogenesis or treatment remains unclear. Research into molecular profiles and validation of prognostic or predictive biomarkers will be required to identify patient subsets most likely to experience meaningful benefit from this important class of agents.
https://ift.tt/2DML0Tq
Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer
Purpose: Increasing number of castration-resistant prostate cancer (CRPC) tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor prognosis and its development is poorly understood. Experimental Design: We applied mass spectrometry-based proteomics to a unique set of 17 prostate cancer patient-derived xenografts (PDX) to characterize the effects of castration in vivo, and the proteome differences between NEPC and prostate adenocarcinomas. Genome-wide profiling of REST occupied regions in prostate cancer cells were correlated to the expression changes in vivoto investigate the role of the transcriptional repressor REST in castration-induced NEPC differentiation. Results: An average of 4881 proteins were identified and quantified from each PDX. Proteins related to neurogenesis, cell cycle regulation and DNA repair were found upregulated elevated in NEPC, while the reduced levels of proteins involved in mitochondrial functions suggested a prevalent glycolytic metabolism of NEPC tumors. Integration of the REST chromatin bound regions with expression changes indicated a direct role REST in regulating neuronal gene expression in prostate cancer cells. Mechanistically, depletion of REST led to cell cycle arrest in G1, which could be rescued by p53 knockdown. Finally, the expression of the REST regulated gene Secretagogin (SCGN), correlated with in increased risk of suffering disease relapse after radical prostatectomy. Conclusions: This study presents the first deep characterization of the proteome of NEPC and suggests that concomitant inhibition of REST and p53 pathway would promote NEPC. We also identify SCGN as a novel prognostic marker in prostate cancer.
https://ift.tt/2zLk5mT
Robust activity of avapritinib, potent and highly selective inhibitor of mutated KIT, in patient-derived xenograft models of gastrointestinal stromal tumors
Purpose: Gastrointestinal stromal tumors (GIST) are commonly treated with tyrosine kinase inhibitors (TKI). The majority of patients with advanced GIST ultimately become resistant to TKI due to acquisition of secondary KIT mutations, while primary resistance is mainly caused by PDGFRA p.D842V mutation. We tested the activity of avapritinib, potent and highly selective inhibitor of mutated KIT and PDGFRA, in three patient-derived xenograft (PDX) GIST models carrying different KIT mutations, with differential sensitivity to standard TKI. Experimental Design: NMRI nu/nu mice (n=93) were transplanted with human GIST xenografts with KIT exon 11+17 (UZLX-GIST9KIT11+17), exon 11 (UZLX-GIST3KIT11) or exon 9 (UZLX-GIST2BKIT9) mutations, respectively. We compared avapritinib (10 and 30 mg/kg/qd) vs. vehicle, imatinib (50 mg/kg/bid) or regorafenib (30 mg/kg/qd) [UZLX-GIST9KIT11+17]; avapritinib (10, 30, 100 mg/kg/qd) vs. vehicle or imatinib [UZLX-GIST3KIT11]; and avapritinib (10, 30, 60 mg/kg/qd) vs. vehicle, imatinib (50, 100 mg/kg/bid) or sunitinib (40 mg/kg/qd) [UZLX-GIST2BKIT9].Results: In all models avapritinib resulted in reduction of tumor volume, significant inhibition of proliferation and reduced KIT signaling. In two models, avapritinib led to remarkable histologic responses, increase in apoptosis and inhibition of MAPK-phosphorylation. Avapritinib showed superior (UZLX-GIST9KIT 11+17 and -GIST2BKIT9) or equal (UZLX-GIST3KIT11) anti-tumor activity to standard dose of imatinib. In UZLX-GIST9KIT11+17, the anti-tumor effects of avapritinib were significantly better than with imatinib or regorafenib. Conclusions: Avapritinib has significant anti-tumor activity in GIST PDX models characterized by different KIT mutations and sensitivity to established TKI. These data provide strong support for ongoing clinical trials with avapritinib in patients with GIST (NCT02508532, NCT03465722).
https://ift.tt/2DLNIZb
TET2 deficiency causes germinal center hyperplasia, impairs plasma cell differentiation and promotes B-cell lymphomagenesis [Research Articles]
TET2 somatic mutations occur in ~10% of DLBCLs but are of unknown significance. Herein we show that TET2 is required for the humoral immune response and is a DLBCL tumor suppressor. TET2 loss of function disrupts transit of B-cells through germinal centers (GC), causing GC hyperplasia, impaired class switch recombination, blockade of plasma cell differentiation and a pre-neoplastic phenotype. TET2 loss was linked to focal loss of enhancer hydroxymethylation and transcriptional repression of genes that mediate GC exit such as PRDM1. Notably, these enhancers and genes are also repressed in CREBBP-mutant DLBCLs. Accordingly, TET2 mutation in patients yields a CREBBP-mutant gene expression signature, CREBBP and TET2 mutations are generally mutually exclusive, and hydroxymethylation loss caused by TET2 deficiency impairs enhancer H3K27 acetylation. Hence TET2 plays a critical role in the GC reaction and its loss of function results in lymphomagenesis through failure to activate genes linked to GC exit signals
https://ift.tt/2zKnN04
Intermittent Hypoxemia in Infants Born Late Preterm: A Prospective Cohort Observational Study
To determine if late preterm infants are at increased risk of intermittent hypoxemic events compared with term infants.
https://ift.tt/2OnSMXZ
Adverse Childhood Experiences and Weight Status among Adolescents
To investigate the relationship between adverse childhood experiences (ACEs) and weight status among adolescents.
https://ift.tt/2P3dppe
Pathogenesis, Genetics, and Genomics of Non–High Grade Serous Ovarian Cancers
The 5 main non–high grade serous epithelial ovarian cancers (clear cell, low grade endometrioid, low grade serous, mucinous, and carcinosarcoma) are discrete in terms of their pathogenesis, molecular biology, and treatment sensitivity. This article reviews the current understanding of their pathogenesis and molecular biology, highlighting areas of uncertainty where future research efforts should be focused.
https://ift.tt/2NWZswH
Emerging Role and Future Directions of Immunotherapy in Advanced Ovarian Cancer
Clinical progress in cancer immunotherapy has been slow; however, within the last 5 years, breakthrough successes have brought immunotherapy to the forefront in cancer therapy. Promising results have been observed in solid tumors and hematologic malignancies. Most treatment modalities have shown limited efficacy as monotherapy. The complex nature of cancer and the immunosuppressive microenvironment emphasizes the need to personalize immunotherapy by manipulating the patient's own immune system. For successful and long-lasting cure of cancer, a multimodal approach is essential, combining antitumor cell therapy with manipulation of multiple pathways in the tumor microenvironment to ameliorate tumor-induced immunosuppression.
https://ift.tt/2NkA52U
Antibody Drug Conjugates in the Treatment of Epithelial Ovarian Cancer
Antibody drug conjugates are novel mechanisms for delivering chemotherapy. They vary based on the targeted antigen, conjugated cytotoxic, and the type of linker used. These differences determine what cells are targeted. There are 2 antibody drug conjugates approved for use in cancer. For epithelial ovarian cancer, more than 15 antibody drug conjugates are under study. Using antibody drug conjugates in epithelial ovarian cancer makes sense. This review discusses promising trial results demonstrating efficacy. Reported toxicities include visual disturbance. There is an absence of significant hematologic toxicity. Overlapping toxicity between standard cytotoxics and antibody drug conjugates includes neuropathy and constitutional symptoms.
https://ift.tt/2NVQTlD
Catestatin Induces Glucose Uptake and GLUT4 Trafficking in Adult Rat Cardiomyocytes
Catestatin is a cationic and hydrophobic peptide derived from the enzymatic cleavage of the prohormone Chromogranin A. Initially identified as a potent endogenous nicotinic–cholinergic antagonist, Catestatin has recently been shown to act as a novel regulator of cardiac function and blood pressure and as a cardioprotective agent in both pre- and postconditioning through AKT-dependent mechanisms. The aim of this study is to investigate the potential role of Catestatin also on cardiac metabolism modulation, particularly on cardiomyocytes glucose uptake. Experiments were performed on isolated adult rat cardiomyocytes. Glucose uptake was assessed by fluorescent glucose incubation and confocal microscope analysis. Glut4 plasma membrane translocation was studied by immunofluorescence experiments and evaluation of the ratio peripheral vs internal Glut4 staining. Furthermore, we performed immunoblot experiments to investigate the involvement of the intracellular pathway AKT/AS160 in the Catestatin dependent Glut4 trafficking. Our results show that 10 nM Catestatin induces a significant increase in the fluorescent glucose uptake, comparable to that exerted by 100 nM Insulin. Moreover, Catestatin stimulates Glut4 translocation to plasma membrane and both AKT and AS160 phosphorylation. All these effects were inhibited by Wortmannin. On the whole, we show for the first time that Catestatin is able to modulate cardiac glucose metabolism, by inducing an increase in glucose uptake through Glut4 translocation to the plasma membrane and that this mechanism is mediated by the AKT/AS160 intracellular pathway.
https://ift.tt/2IvxamY
Blood Lactate or Lactate Clearance: Which Is Robust to Predict the Neurological Outcomes after Cardiac Arrest? A Systematic Review and Meta-Analysis
Aims. Lactate and lactate clearance were supposed to be associated with cardiac arrest outcomes, but studies obtained different results. Thus, we conducted this meta-analysis to investigate the association between lactate or lactate clearance and neurological outcomes and their usefulness for prediction of neurological outcomes. Methods. We conducted a systematic search in PubMed, Web of science, EMBASE, Medline, and Google Scholar until May 1, 2018, for relevant studies. Studies reporting lactate, lactate clearance on admission, or other time points after admission associated with neurological outcomes were included in our analysis. Pooled effect date was shown as weighed mean difference (WMD) and 95% confidence interval (CI). To measure the usefulness of lactate on admission to predict neurological outcomes, we also pooled the data of diagnostic test. Results. 23 studies involving 6720 cardiac arrest (CA) patients were included. Results from our analysis indicated that patients with good neurological outcomes tended to have a lower lactate level on admission (WMD: -2.66 mmol/L, 95%CI: -3.39 to -1.93) and 12h, 24h, and 48h after admission (P
https://ift.tt/2zKbTTS
Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in Burkitt lymphoma
Abstract
Purpose
Burkitt's lymphoma (BL) is an aggressive lymphoma subtype with high 18F-FDG avidity at 18F-FDG-PET/CT, but no validated criteria for PET/CT in treatment evaluation or prediction of outcome in BL are available. The aim of our study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in BL.
Materials and methods
We retrospectively enrolled 65 patients who underwent baseline 18F-FDG-PET/CT, interim and end of treatment PET/CT. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), the maximum standardized uptake value lean body mass (SUVlbm), the maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), total metabolic tumor volume (tMTV) and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan–Meier method.
Results
At a median follow-up of 40 months, the median PFS and OS were 34 and 39 months. MTV and TLG were significantly higher in patients with partial response compared to complete response group at end of treatment, while no significant differences were found at interim. Other metabolic PET/CT parameters were not related to treatment response. MTV and TLG were demonstrated to be independent prognostic factors for both PFS and OS; instead SUVbw, SUVlbm, SUVbsa, L-L SUV R and L-BP SUV R were not related to outcome survival.
Conclusions
Metabolic tumour features (MTV and TLG) were significantly correlated with response to treatment and long-term outcome.
https://ift.tt/2zJMOZl
TRK Inhibition: A New Tumor-Agnostic Treatment Strategy
Abstract
Oncogenic somatic chromosomal rearrangements involving the NTRK1, NTRK2 or NTRK3 genes (NTRK gene fusions) occur in up to 1% of all solid tumors, and have been reported across a wide range of tumor types. The fusion proteins encoded by such rearranged sequences have constitutively activated TRK tyrosine kinase domains, providing novel therapeutic anticancer targets. The potential clinical effectiveness of TRK inhibition in patients with tumors harboring NTRK gene fusions is being assessed in phase I and II trials of TRK inhibitors, such as larotrectinib and entrectinib. Clinical trial results have demonstrated that larotrectinib is generally well tolerated and has shown high response rates that are durable across tumor types. These data validate NTRK gene fusions as actionable genomic alterations. In this review, we present the clinical data, discuss the different approaches that might be used to routinely screen tumors to indicate the presence of NTRK gene fusions, explore the issue of acquired resistance to TRK inhibition, and reflect on the wider regulatory considerations for tumor site agnostic TRK inhibitor drug development.
https://ift.tt/2NecZux
Firefly Tips and Tricks: Windows 10 Camera Privacy Settings
A recent Windows release has made a minor adjustment to some computer Camera Privacy Settings. If your computer has been affected, your FireflyPro application will open like the image below:
In order to resolve the issue, you will need to make one small adjustment:
- Go to your Camera Privacy Settings.
- Go to "Allow apps to access your camera"
- Change this setting from "Off" to "On".
FireflyPro should now open correctly!
https://ift.tt/2NgMpRp
New Research From Clinical Psychological Science
Read about the research published in Clinical Psychological Science:
A Model of the Intersection of Pain and Opioid Misuse in Children and Adolescents
Genevieve F. Dash, Anna C. Wilson, Benjamin J. Morasco, and Sarah W. Feldstein Ewing
This review addresses the role of pain and pediatric opioid prescriptions in potentiating the risk of opioid misuse. In medical settings, youths are not routinely prescribed substances they might abuse, except for opioids: Almost 20% of high school students have received at least one opioid prescription by their senior year. The introduction of opioids via prescription might contribute to the development of opioid-induced hyperalgesia (increased sensitivity to pain), chronic pain, and disability, leading to increased opioid use and opioid-related problems. Youth are at a higher risk for these outcomes if, before the prescription, they already suffered from psychological distress, pain, and disability and were unable to deal with distress. Their peers also use opioids without fully perceiving the risk; their parents suffer from chronic pain, use opioids or other drugs, and show low parental monitoring. Other risk factors include available household and peer opioid prescriptions, higher opioid prescription doses and refills, as well as persistent pain, pain catastrophizing, and a pleasurable "high" from opioids. Pain self-efficacy (confidence in one's ability to function while in pain), the use of nonpharmacological pain treatments, and non-substance-using friends might be factors protecting against opioid misuse.
Meta-Awareness of Dysregulated Emotional Attention
Liad Ruimi, Yuval Hadash, Ariel Zvielli, Iftach Amir, Pavel Goldstein, and Amit Bernstein
Meta-awareness of attentional biases (MAB) — self-awareness that one's attentional processing of emotional information is dysregulated – may help individuals regulate attention to emotional stimuli. Ruimi et al. examined cigarette smokers' attentional biases, asking them to rapidly identify the location of probes on a screen; the researchers manipulated whether the probe appeared in the same location as neutral images (e.g., a pencil) or appetitive images (e.g., a cigarette). During the task, participants responded to questions, reporting whether one of the images in the previous trial attracted their attention and influenced their response. Results revealed individual differences in MAB. When people showed attentional bias on one trial, momentary absence of MAB was associated with subsequent attentional bias in the opposite direction on the following trial, a sign of dysregulation. Momentary presence of MAB reduced this reactivity and was more likely to be followed by balanced attentional allocation. This study introduces a method for objectively estimating MAB and provides evidence for a functional link between MAB and attentional processing of reward cues.
Bereavement Outcomes as Causal Systems: A Network Analysis of the Co-Occurrence of Complicated Grief and Posttraumatic Growth
Benjamin W. Bellet, Payton J. Jones, Robert A. Neimeyer, and Richard J. McNally
The loss of a loved one can lead to complicated grief (CG), a debilitating yearning for the deceased. But mourners who experience CG often also experience posttraumatic growth (PTG). To investigate how CG and PTG are connected, Bellet and colleagues investigated the structure of the network of CG and PTG elements, in which symptoms are represented by nodes, and associations among nodes are represented by links with different thicknesses signifying the strength of the association. The authors surveyed 485 participants who had lost a loved one within the past 2 years and computed CG and PTG networks, identified the central features of each one, and then computed a network of both CG and PTG. The results indicate that challenges to control and identity disturbance are the most central elements of CG, whereas the discovery of a new life path and greater personal strength are the most central elements of PTG. CG and PTG shared positive and negative links, and the most central element that seemed to connect them was the degree of disruption and change in mourner's world views. These results suggest that being negatively affected by someone's death may promote personal growth.
Ventrolateral Prefrontal Cortex Activation During Social Exclusion Mediates the Relation Between Intolerance of Uncertainty and Trait Aggression
Stephanie M. Gorka, K. Luan Phan, Bobak Hosseini, Eunice Y. Chen, and Michael S. McCloskey
To test whether intolerance of uncertainty (IU) is associated with aggression as a behavioral trait via the activation of the ventrolateral prefrontal cortex (vlPFC), Gorka and colleagues assessed brain activity in patients with intermittent explosive disorder and in nonpatients during a social-exclusion task. The authors used Cyberball, a virtual game in which participants are instructed to play a ball-tossing game with two other participants; in reality, however, the actions of the other players are computer-controlled and designed to induce social inclusion (the ball is tossed to the participant) or exclusion (the two other players do not toss the ball to the participant). In addition, Gorka et al. collected measures of IU and lifetime history of aggression (LHA). The results indicated that greater LHA was associated with prospective IU (i.e., excessive worry about the future) but not with inhibitory IU (i.e., avoidance behaviors), and greater prospective IU was associated with less vlPFC activation during social exclusion. A mediation model indicated an indirect effect of prospective IU on LHA through vlPFC activation, suggesting that individuals with high IU might have difficulties in neural regulation, which may increase propensity for aggression.
Central Sensitization: Explanation or Phenomenon?
Emanuel N. van den Broeke, Diana M. Torta, and Omer Van den Bergh
Central sensitization (CS) has been used in pain research to explain pain hypersensitivity in conditions such as whiplash and chronic pain; recently, some researchers have applied CS to nonpain symptoms, such as anxiety or depression. In this commentary, van den Broeke and colleagues point out that generalizing CS explanations to nonpain symptoms adds a label without actually explaining those symptoms. As defined by the International Association for the Study of Pain, CS refers to the increased responsiveness of a group of sensory neurons that receives information about potentially damaging stimuli and sends signals resulting in the physical sensation of pain. Therefore, the authors say, CS does not apply to increased responsiveness to stimuli that are not related to physical pain and does not explain enhanced responsiveness to emotionally relevant stimuli. They also suggest that the role of cognitive and emotional factors should be considered as potential explanations for these phenomena.
https://ift.tt/2DI8s42
Head and Neck Cancer: Improving Patient-Reported Outcome Measures for Clinical Practice
Opinion statement
Head and neck cancer includes a wide range of tumors that occur in several areas of the upper aerodigestive tract. Most head and neck cancer patients report treatment-related late effects (both physical and psycho-social). High-quality and patient-centered care in head and neck cancer depend on the understanding of the continuum patient's experience—the disease pathway. Healthcare has been improved by involving patients more actively in the disease process, and a few reports support that patient-reported outcomes—built around the patient's experience—given in a timely manner to oncologists are extremely valuable in oncology clinical care. Implementation and clinical use of patient-reported outcomes requires some procedures involving head and neck cancer patients, clinicians, researchers, and institutional leaders The unified and integrated vision is still absent and some current concerns are being discussed to optimize benefits of patient-reported outcomes use in clinical practice. The inclusion of all first-line caregivers, team formation and training, continuous monitoring improvement, and analysis are critical success factors to consider. Our team developed a broader and inclusive understanding of patient-reported outcomes. Patient-reported outcome (Health-Related Quality of Life) assessment is implemented as a systematic and routine process in Head and Neck Unit. Head and neck cancer patients consider the questionnaire administration as part of the clinical approach. We are currently working in a program (PROimp) using mathematical models to identify common head and neck cancer patterns and building prognostic predictive models, to predict future outcomes, to appraise risk/benefit of treatments (standard or new), and to estimate patient's risk of future disease development. It is our aim to better comprehend the singular and unexpected perceptions to really provide directed and personalized cancer care defining the patient pathway. The future holds promising for PROs that are ascending as a nuclear outcome in head and neck oncology.
https://ift.tt/2IwRQLp
Influence of Varying Quantitative Fecal Immunochemical Test Positivity Thresholds on Colorectal Cancer Detection A Community-Based Cohort Study
Background:
The fecal immunochemical test (FIT) is commonly used for colorectal cancer (CRC) screening. Despite demographic variations in stool hemoglobin concentrations, few data exist regarding optimal positivity thresholds by age and sex. Objective:
To identify programmatic (multitest) FIT performance characteristics and optimal FIT quantitative hemoglobin positivity thresholds in a large, population-based, screening program. Design:
Retrospective cohort study. Setting:
Kaiser Permanente Northern and Southern California. Participants:
Adults aged 50 to 75 years who were eligible for screening and had baseline quantitative FIT results (2013 to 2014) and 2 years of follow-up. Nearly two thirds (411 241) had FIT screening in the previous 2 years. Measurements:
FIT programmatic sensitivity for CRC and number of positive test results per cancer case detected, overall and by age and sex. Results:
Of 640 859 persons who completed a baseline FIT and were followed for 2 years, 481 817 (75%) had at least 1 additional FIT and 1245 (0.19%) received a CRC diagnosis. Cancer detection (programmatic sensitivity) increased at lower positivity thresholds, from 822 in 1245 (66.0%) at 30 µg/g to 925 (74.3%) at 20 µg/g and 987 (79.3%) at 10 µg/g; the number of positive test results per cancer case detected increased from 43 at 30 µg/g to 52 at 20 µg/g and 85 at 10 µg/g. Reducing the positivity threshold from 20 to 15 µg/g would detect 3% more cancer cases and require 23% more colonoscopies. At the conventional FIT threshold of 20 µg/g, programmatic sensitivity decreased with increasing age (79.0%, 73.4%, and 68.9% for ages 50 to 59, 60 to 69, and 70 to 75 years, respectively; P = 0.009) and was higher in men than women (77.0% vs. 70.6%; P = 0.011). Limitation:
Information on advanced adenoma was lacking. Conclusion:
Increased cancer detection at lower positivity thresholds is counterbalanced by substantial increases in positive tests. Tailored thresholds may provide screening benefits that are more equal among different demographic groups, depending on local resources. Primary Funding Source:
National Cancer Institute.https://ift.tt/2OxwhfY
Prevalence and Distribution of E-Cigarette Use Among U.S. Adults: Behavioral Risk Factor Surveillance System, 2016
Background:
Contemporary data on the prevalence of e-cigarette use in the United States are limited. Objective:
To report the prevalence and distribution of current e-cigarette use among U.S. adults in 2016. Design:
Cross-sectional. Setting:
Behavioral Risk Factor Surveillance System, 2016. Participants:
Adults aged 18 years and older. Measurements:
Prevalence of current e-cigarette use by sociodemographic groups, comorbid medical conditions, and states of residence. Results:
Of participants with information on e-cigarette use (n = 466 842), 15 240 were current e-cigarette users, representing a prevalence of 4.5%, which corresponds to 10.8 million adult e-cigarette users in the United States. Of the e-cigarette users, 15% were never–cigarette smokers. The prevalence of current e-cigarette use was highest among persons aged 18 to 24 years (9.2% [95% CI, 8.6% to 9.8%]), translating to approximately 2.8 million users in this age range. More than half the current e-cigarette users (51.2%) were younger than 35 years. In addition, the age-standardized prevalence of e-cigarette use was high among men; lesbian, gay, bisexual, and transgender (LGBT) persons; current combustible cigarette smokers; and those with chronic health conditions. The prevalence of e-cigarette use varied widely among states, with estimates ranging from 3.1% (CI, 2.3% to 4.1%) in South Dakota to 7.0% (CI, 6.0% to 8.2%) in Oklahoma. Limitation:
Data were self-reported, and no biochemical confirmation of tobacco use was available. Conclusion:
E-cigarette use is common, especially in younger adults, LGBT persons, current cigarette smokers, and persons with comorbid conditions. The prevalence of use differs across states. These contemporary estimates may inform researchers, health care policymakers, and tobacco regulators about demographic and geographic distributions of e-cigarette use. Primary Funding Source:
American Heart Association Tobacco Regulation and Addiction Center, which is funded by the U.S. Food and Drug Administration and National Heart, Lung, and Blood Institute.https://ift.tt/2PdLy5H
Chronic Pain Among Suicide Decedents, 2003 to 2014: Findings From the National Violent Death Reporting System
Background:
More than 25 million adults in the United States have chronic pain. Chronic pain has been associated with suicidality, but previous studies primarily examined nonfatal suicidal behaviors rather than suicide deaths associated with chronic pain or the characteristics of such deaths. Objective:
To estimate the prevalence of chronic pain among suicide decedents in a large multistate sample and to characterize suicide decedents with and without chronic pain. Design:
Retrospective analysis of National Violent Death Reporting System (NVDRS) data. The NVDRS links death certificate, coroner or medical examiner, and law enforcement data collected by investigators, who often interview informants who knew the decedent to gather information on precipitating circumstances surrounding the suicide. Information is abstracted by using standard coding guidance developed by the Centers for Disease Control and Prevention. Setting:
18 states participating in the NVDRS. Participants:
Suicide decedents with and without chronic pain who died during 1 January 2003 to 31 December 2014. Measurements:
Demographic characteristics, mechanism of death, toxicology results, precipitating circumstances (mental health, substance use, interpersonal problems, life stressors), and suicide planning and intent. Results:
Of 123 181 suicide decedents included in the study, 10 789 (8.8%) had evidence of chronic pain, and the percentage increased from 7.4% in 2003 to 10.2% in 2014. More than half (53.6%) of suicide decedents with chronic pain died of firearm-related injuries and 16.2% by opioid overdose. Limitation:
The results probably underrepresent the true percentage of suicide decedents who had chronic pain, given the nature of the data and how they were captured. Conclusion:
Chronic pain may be an important contributor to suicide. Access to quality, comprehensive pain care and adherence to clinical guidelines may help improve pain management and patient safety. Primary Funding Source:
None.https://ift.tt/2x4a1Tv
Treatments of Primary Basal Cell Carcinoma of the Skin A Systematic Review and Network Meta-analysis
Background:
Most interventions for basal cell carcinoma (BCC) have not been compared in head-to-head randomized trials. Purpose:
To evaluate the comparative effectiveness and safety of treatments of primary BCC in adults. Data Sources:
English-language searches of MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase from inception to May 2018; reference lists of guidelines and systematic reviews; and a search of ClinicalTrials.gov in August 2016. Study Selection:
Comparative studies of treatments currently used in adults with primary BCC. Data Extraction:
One investigator extracted data on recurrence, histologic clearance, clinical clearance, cosmetic outcomes, quality of life, and mortality, and a second reviewer verified extractions. Several investigators evaluated risk of bias for each study. Data Synthesis:
Forty randomized trials and 5 nonrandomized studies compared 18 interventions in 9 categories. Relative intervention effects and mean outcome frequencies were estimated using frequentist network meta-analyses. Estimated recurrence rates were similar for excision (3.8% [95% CI, 1.5% to 9.5%]), Mohs surgery (3.8% [CI, 0.7% to 18.2%]), curettage and diathermy (6.9% [CI, 0.9% to 36.6%]), and external-beam radiation (3.5% [CI, 0.7% to 16.8%]). Recurrence rates were higher for cryotherapy (22.3% [CI, 10.2% to 42.0%]), curettage and cryotherapy (19.9% [CI, 4.6% to 56.1%]), 5-fluorouracil (18.8% [CI, 10.1% to 32.5%]), imiquimod (14.1% [CI, 5.4% to 32.4%]), and photodynamic therapy using methyl-aminolevulinic acid (18.8% [CI, 10.1% to 32.5%]) or aminolevulinic acid (16.6% [CI, 7.5% to 32.8%]). The proportion of patients reporting good or better cosmetic outcomes was better for photodynamic therapy using methyl-aminolevulinic acid (93.8% [CI, 79.2% to 98.3%]) or aminolevulinic acid (95.8% [CI, 84.2% to 99.0%]) than for excision (77.8% [CI, 44.8% to 93.8%]) or cryotherapy (51.1% [CI, 15.8% to 85.4%]). Data on quality of life and mortality were too sparse for quantitative synthesis. Limitation:
Data are sparse, and effect estimates are imprecise and informed by indirect comparisons. Conclusion:
Surgical treatments and external-beam radiation have low recurrence rates for the treatment of low-risk BCC, but substantial uncertainty exists about their comparative effectiveness versus other treatments. Gaps remain regarding high-risk BCC subtypes and important outcomes, including costs. Primary Funding Source:
Agency for Healthcare Research and Quality. (PROSPERO: CRD42016043353).https://ift.tt/2QEjXMs
PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation
Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation. The checklist was developed by a 24-member expert panel and 2 research leads following published guidance from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. The final checklist contains 20 essential reporting items and 2 optional items. The authors provide a rationale and an example of good reporting for each item. The intent of the PRISMA-ScR is to help readers (including researchers, publishers, commissioners, policymakers, health care providers, guideline developers, and patients or consumers) develop a greater understanding of relevant terminology, core concepts, and key items to report for scoping reviews.
https://ift.tt/2PWtUo9
Caring for Those Who Serve: Potential Implications of the Veterans Affairs Maintaining Internal Systems and Strengthening Integrated Outside Networks Act of 2018
The Veterans Affairs Maintaining Internal Systems and Strengthening Integrated Outside Networks Act of 2018 removes barriers to veterans' access to community-based health care providers and permanently establishes the commercial health care marketplace as another provider of health care to veterans. This commentary discusses the implications of expanding private sector health care for veterans on veterans' health care experiences and outcomes and on the Veterans Affairs health system.
https://ift.tt/2NFhTl2
https://ift.tt/2NFhTl2
Clinical–Community Partnerships to Reduce Food Insecurity Among High-Need, High-Cost Medicaid Patients
Limited or uncertain access to adequate food is associated with adverse health consequences. Although federal programs, such as the Supplemental Nutrition Assistance Program, aim to improve access to healthy food for low-income Americans, the current benefits are inadequate for many. In this essay, the authors propose cross-sector partnerships between clinical programs and community-based organizations as a promising approach for addressing food insecurity in the United States.
https://ift.tt/2nVbh7c
https://ift.tt/2nVbh7c
Data Are Needed on the Potential Adverse Effects of Marijuana Use in Pregnancy
Marijuana use during pregnancy is increasing, and any adverse effect on mothers and babies remains unclear. In a cohort of pregnant women in the Kaiser Permanente Northern California health system who were universally screened for prenatal substance use by self-report and urine toxicology, the authors examined the co-use of marijuana with other substances of potential misuse.
https://ift.tt/2ORimRG
https://ift.tt/2ORimRG
Annals Understanding Clinical Research: Interpreting Results With Large P Values
Relying solely on P values to interpret study results is widely recognized as suboptimal, but it remains the dominant method of study interpretation in biomedicine. This tutorial discusses issues to consider and misinterpretations to avoid when encountering P values greater than 0.05.
https://ift.tt/2oVcFXW
https://ift.tt/2oVcFXW
Gastrointestinal juvenile-like (inflammatory/hyperplastic) mucosal polyps in neurofibromatosis type 1 with no concurrent genetic or clinical evidence of other syndromes
Abstract
Gastrointestinal "juvenile-like (inflammatory/hyperplastic) mucosal polyps" (JLIHMPs) have been proposed as a neurofibromatosis type 1 (NF1)-specific gastrointestinal manifestation. Juvenile polyposis syndrome (JPS) has also been reported in a NF1 patient, harboring concurrent NF1 and SMAD4 germline mutations. Additionally, NF1-like cafe-au-lait spots have been described in biallelic mismatch repair deficiency, another condition featuring gastrointestinal polyps. The SMAD4 and BMPR1A genes that are involved in 50–60% of JPS cases have not been investigated in the ~ 20 published cases of NF1-associated JLIHMPs with the exception of the abovementioned patient with concomitant JPS and NF1. NF1 defects have been found in the only two cases exhaustively tested. Therefore, JLIHMP has been questioned as an independent, NF1-specific entity. Incidental associations between NF1 and gastrointestinal polyposes at risk for gastrointestinal carcinoma should not be overlooked, given their implications in terms of clinical surveillance. We describe two patients featuring JLIHMPs in clinically/genetically proven NF1, in the absence of SMAD4 and BMPR1A mutations. In one case, the intervening mucosa was markedly inflamed, unlike JPS. We suggest that JLIHMP probably represents a gastrointestinal lesion specific to NF1.
https://ift.tt/2Ox17sw
Listeria monocytogenes Infection of the Brain
During infection, Listeria monocytogenes is capable of crossing the blood-brain barrier to colonize the brain. In this protocol, we demonstrate how to assess bacterial colonization of organs following infection of mice. A procedure to perform whole organ perfusion for specific determination of bacterial numbers in the brain parenchyma is provided.
https://ift.tt/2DN2MG1
Isolation, Fixation, and Immunofluorescence Imaging of Mouse Adrenal Glands
Here we present a method to isolate adrenal glands from mice, fix the tissues, section them, and perform immunofluorescence staining.
https://ift.tt/2zKqkYe
Spotlight: QinFlow features the Warrior – a next generation portable blood and IV fluid warmer
QinFlow's mission is to help save lives across the entire continuum of emergency care.
https://ift.tt/2NfIvsf
A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome
https://ift.tt/2y7xrHW
Identification and characterization of N-glycosylation site on a Mucor circinelloides aspartic protease expressed in Pichia pastoris: effect on secretion, activity and thermo-stability
Methylotrophic yeasts have widely been used as model organisms for understanding cellular functions and biochemical activities in lower eukaryotes. The gene encoding an aspartic protease (MCAP) from Mucor circine...
https://ift.tt/2NUGtmD
Microbial community dynamics in an ANAMMOX reactor for piggery wastewater treatment with startup, raising nitrogen load, and stable performance
Bacterial community dynamics of the ANAMMOX reactor of an integrated "UASB + SHARON + ANAMMOX" system for treating piggery wastewater were investigated using the Illumina MiSeq method with samples obtained at ...
https://ift.tt/2y52Evt
Berberine attenuate staphylococcal enterotoxin B-mediated acute liver injury via regulating HDAC expression
Staphylococcal enterotoxin B (SEB) has been documented to be implicated in the pathogenesis of liver injury in the experimental models of hepatitis. However, the underlying mechanism of SEB-induced acute liver...
https://ift.tt/2NXzJnI
Readmission, Death Risk Higher in COPD With Comorbidities
MONDAY, Oct. 1, 2018 -- Patients with chronic obstructive pulmonary disease (COPD) who have comorbidities are more likely to experience readmission or mortality and less likely to receive beneficial treatments, according to a study published in the...
https://ift.tt/2QnQxBb
Risk of Relapse Up for Teens, Young Adults With Leukemia
MONDAY, Oct. 1, 2018 -- Adolescents and young adults (AYA; aged 15 to 39 years) with acute lymphoblastic leukemia (ALL) have increased risk of on-therapy relapse and relapse after completing therapy compared with children with ALL, according to a...
https://ift.tt/2zJOIcs
Hospital Privacy Curtains Become Increasingly Contaminated
MONDAY, Oct. 1, 2018 -- Curtains surrounding patient beds become progressively contaminated with bacteria, according to a study published in the September issue of the American Journal of Infection Control. Kevin Shek, from the University of...
https://ift.tt/2zIMqdm
Genetics May Identify Type 2 Diabetes Subtypes
MONDAY, Oct. 1, 2018 -- Clusters of type 2 diabetes (T2D) loci and traits have been identified, according to a study published online Sept. 21 in PLOS Medicine. Miriam S. Udler, M.D., Ph.D., from Massachusetts General Hospital in Boston, and...
https://ift.tt/2QnQsNT
Intravitreal Triamcinolone Beats Periocular Tx for Macular Edema
MONDAY, Oct. 1, 2018 -- For patients with uveitic macular edema (ME), intravitreal triamcinolone acetonide (ITA) and intravitreal dexamethasone implant (IDI) are superior to periocular triamcinolone acetonide (PTA), according to a study published...
https://ift.tt/2zIMnyc
Anti-Reflux Surgery Promising in Idiopathic Pulmonary Fibrosis
MONDAY, Oct. 1, 2018 -- Laparoscopic antireflux surgery is safe and well-tolerated in patients with idiopathic pulmonary fibrosis (IPF) and abnormal acid gastroesophageal reflux (GER), according to a phase 2 study published in the Sept. 1 issue of...
https://ift.tt/2QnQqpf
Factors Associated With Phantom Odor Identified
MONDAY, Oct. 1, 2018 -- Phantom odor perception in middle-aged and older individuals is associated with poor health, persistent dry mouth, and head injury, according to a study published online Aug. 16 in JAMA Otolaryngology-Head & Neck...
https://ift.tt/2zIMidS
More Non-Elderly Americans Uninsured in 2017 Versus 2016
MONDAY, Oct. 1, 2018 -- From 2016 to 2017, there was an increase in the number of uninsured non-elderly Americans, according to a report published by the Robert Wood Johnson Foundation. Laura Skopec, from the Urban Institute's Health Policy Center...
https://ift.tt/2QnQplb
Mental Health Disparities ID'd Among Students of Color
MONDAY, Oct. 1, 2018 -- College students of color have lower mental health-related treatment use relative to white students, according to a study published in the September issue of the Journal of Adolescent Health. Sarah Ketchen Lipson, Ph.D., from...
https://ift.tt/2zJwZlm
September 2018 Briefing - Surgery
Here are what the editors at HealthDay consider to be the most important developments in Surgery for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...
https://ift.tt/2QnQmWx
September 2018 Briefing - Otolaryngology
Here are what the editors at HealthDay consider to be the most important developments in Otolaryngology for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes...
https://ift.tt/2zJ1cB5
September 2018 Briefing - Allergy
Here are what the editors at HealthDay consider to be the most important developments in Allergy for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...
https://ift.tt/2QnQkOp
September 2018 Briefing - Internal Medicine
Here are what the editors at HealthDay consider to be the most important developments in Internal Medicine for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes...
https://ift.tt/2zJtDPp
September 2018 Briefing - Urology
Here are what the editors at HealthDay consider to be the most important developments in Urology for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...
https://ift.tt/2QnQkhn
September 2018 Briefing - Neurology
Here are what the editors at HealthDay consider to be the most important developments in Neurology for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...
https://ift.tt/2zJuBLb
September 2018 Briefing - Orthopedics
Here are what the editors at HealthDay consider to be the most important developments in Orthopedics for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...
https://ift.tt/2QlL0eA
September 2018 Briefing - Pain Management
Here are what the editors at HealthDay consider to be the most important developments in Pain Management for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes...
https://ift.tt/2zJuzTz
September 2018 Briefing - Pharmacy
Here are what the editors at HealthDay consider to be the most important developments in Pharmacy for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...
https://ift.tt/2QnQeq1
September 2018 Briefing - HIV & AIDS
Here are what the editors at HealthDay consider to be the most important developments in HIV & AIDS for September 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes...
https://ift.tt/2zIMcD2
Computed tomography coronary angiography in patients without known coronary artery disease can demonstrate possible non-cardiovascular causes of non-acute retrosternal chest pain
Abstract
Objectives
To assess the computed tomography coronary angiography (CTCA) accuracy for demonstrating possible non-cardiovascular causes of non-acute retrosternal chest pain in patients without known coronary artery disease (CAD) and to correlate CTCA results with the patient management and relief from pain.
Methods
This prospective observational study was approved by the ethical committee. Consecutive patients suffering non-acute chest pain who underwent CTCA and with not known CAD were enrolled and classified as having coronary diseases (CD) or extracardiac diseases (ECD). Association between age, sex, body mass index (BMI), cardiovascular risk factors, and type of chest pain with CD or ECD was estimated. Correlation between BMI classes and each risk factor was also calculated.
Results
A total of 106 patients (60 males; age 62 ± 14 years [mean ± standard deviation]; mean BMI 27) were enrolled. Hypertension was found in 71/106 (67%); smoking was significantly more frequent among males (p = 0.003) and hypercholesterolemia among females (p = 0.017); hypertension and hypercholesterolemia significantly correlated with age, and hypertension also with BMI. Pain was atypical in 70/106 (66%) patients. The kind of pain did not correlate with disease or gender. CTCA showed possible causes of chest pain in 69/106 (65%) patients; 32/69 (47%) having only CD, 23/69 (33%) only ECD, and 14/69 (20%) both CD and ECD. Prevalence was: hiatal hernia 35/106 (33%); significant CAD 24/106 (23%); myocardial bridging 22/106 (21%). At follow-up of 94/106 (89%) patients, 71/94 (76%) were pain-free, 14/17 (82%) significant CAD had been treated, and only one patient with non-significant CAD was treated after CTCA.
Conclusion
CTCA suggested possible causes of non-acute pain in 65% of patients.
Main messages
• CTCA can either rule in or rule out possible causes of chest pain alternative to CAD.
• Clinically relevant findings were detected in 65% of patients with non-acute chest pain.
• Non-cardiovascular diseases potentially explained symptoms in 35% of patients.
https://ift.tt/2NVT3C2
Tox and Hound – Snakes! Why’d it have to be SNAKES?
by Meghan Spyres Unless you suffer the over appreciated and never-ending summer of southern California, the warm weather season is winding down and fall is settling in. Though many will lament the end of iced coffees, sunny beaches, and carefree summer attire, for many toxicologists, we will quietly lament the end of snake season. Perhaps […]
EMCrit Project by Tox & Hound.
https://ift.tt/2Otoumz
Real Time In Vivo Tracking of Thymocytes in the Anterior Chamber of the Eye by Laser Scanning Microscopy
The goal of the protocol is to show longitudinal intravital real-time tracking of thymocytes by laser scanning microscopy in thymic implants in the anterior chamber of the mouse eye. The transparency of the cornea and vascularization of the graft allows for continuously recording progenitor cell recruitment and mature T-cell egress.
https://ift.tt/2Ov0nnq
Caffeine Extraction, Enzymatic Activity and Gene Expression of Caffeine Synthase from Plant Cell Suspensions
https://ift.tt/2P0cLZF
Tandem DNAzyme for double digestion: a new tool for circRNA suppression
Authors: Ding, Junyao / Zhou, Wenhu / Li, Xiaojing / Sun, Meng / Ding, Jingsong / Zhu, Qubo
https://ift.tt/2NMV97d
Roles of the nucleotide exchange factor and chaperone Hsp110 in cellular proteostasis and diseases of protein misfolding
Authors: Yakubu, Unekwu M. / Morano, Kevin A.
https://ift.tt/2P3l6Mn
Efficacy of Huaier granule in patients with breast cancer
Abstract
Background
Huaier extract has been demonstrated to exhibit potent anti-tumor effects in various types of cancer cells. However, the clinical benefit of Huaier granule in breast cancer has not been reported. In this study, we aimed to evaluate the efficacy of Huaier granule in breast cancer patients.
Methods
Our study included 284 breast cancer patients treated with or without Huaier granule between January 2005 and October 2016 at Qilu Hospital, Shandong University, Jinan, China. Retrospective data obtained included demographics, clinicopathological characteristics, disease-free survival (DFS), serum concentrations of tumor markers, the Karnofsky performance scale (KPS), and incidences of emotional symptoms. DFS was the main outcome measure.
Results
Of the patients included, 144 were classified into the control group and 140 into the Huaier group. Baseline characteristics were well balanced between the study arms. Median DFS was 91.43 months for control group and 112.61 months for Huaier group (hazard ratio (HR) = 2.97, 95% confidence interval (CI) = 1.57–5.61, p < 0.01). After Huaier granule treatment, the serum levels of tumor markers could be reduced to the normal range. In addition, breast cancer patients with Huaier granule treatment had higher KPS scores and less emotional symptoms.
Conclusions
Our data demonstrated that patients orally administrated Huaier granule got longer DFS. Furthermore, Huaier granule could reduce serum tumor markers, improve the functional status, and decrease the incidences of emotional symptoms in breast cancer patients. Therefore, Huaier granule was an effective therapy for women with breast cancer.
https://ift.tt/2DMsIl1
Pulsara CEO to speak at Becker’s Hospital Review Health IT Conference
James Woodson will be joined by other leaders in the industry to address the key opportunities and challenges in health IT today BOZEMAN, Mont. — Pulsara is honored to be represented by its CEO, Dr. James Woodson, at the 4th Annual Health IT + Revenue Cycle Conference on September 19-22 in Chicago. Dr. Woodson, ER Physician and Founder/CEO of Pulsara, has been invited to speak on two...
https://ift.tt/2zJTFSC
Healthcare has a communication problem -- and there's more to the answer than your CC&C solution.
Communication issues in the healthcare industry can be detrimental to patient care, waste time and negatively affect a provider's bottom line. During an August 29 webinar sponsored by Pulsara and hosted by Becker's Hospital Review, James Woodson, MD, founder and CEO of Pulsara, and William Atkinson, PhD, president of Guidon Healthcare Consulting, discussed several communication...
https://ift.tt/2IsSFEZ
Winery owner leads program to prevent deaths by donating AEDs
Ron Rubin launched the "Trained for Saving Lives AED Program," through which he has committed to donating one AED to 450 qualifying wineries
https://ift.tt/2NjvJJm
3 ways telemedicine can increase the reach of your EMS agency
Improve access to care and triage less urgent calls for more efficient use of healthcare resources. "Hi, Ms. Smith, my name is Dr. Jones. The paramedics tell me you're having some chest pain today." This is what it sounds like when your patient first arrives into the emergency department. It's also what it sounds like when you're able to integrate telemedicine into...
https://ift.tt/2xTriQk
Attorney Chris Kelly joins Page, Wolfberg & Wirth
MECHANICSBURG, PA — Page, Wolfberg & Wirth ("PWW"), the Nation's leading EMS industry law firm has announced the addition of G. Christopher Kelly as a full-time attorney, effective October 1st. Mr. Kelly is a nationally-recognized EMS attorney and consultant who will advise PWW's clients on issues of reimbursement, compliance, privacy and more. "Chris brings...
https://ift.tt/2RcMDMK
CRISPR Guide RNA Cloning for Mammalian Systems
Here, a simple, efficient, and cost-effective method of sgRNA cloning is outlined.
https://ift.tt/2xUoyCl
Brain metabolism and related connectivity in patients with acrophobia treated by virtual reality therapy: an 18 F-FDG PET pilot study sensitized by virtual exposure
Abstract
Background
The aim of this pilot study is to investigate the impact of virtual reality exposure therapy (VRET) on brain metabolism and connectivity.
Eighteen patients with acrophobia were assessed by an 18F-FDG PET scan sensitized by virtual exposure before treatment, and nine of them were assessed again after eight sessions of VRET. Statistical Parametric Mapping was used to study the correlations between metabolism and pretherapeutic clinical scores and to compare metabolism before and after VRET (p voxel < 0.005, corrected for cluster volume). Metabolic connectivity was evaluated through interregional correlation analysis.
Results
Before therapy, a positive correlation was found between scores on the behavioural avoidance test and left occipital metabolism (BA17-18). After VRET, patients presented increased metabolism in the left frontal superior gyri and the left precentral gyrus, which showed increased metabolic connectivity with bilateral occipital areas (BA17-18-19), concomitant with clinical recovery.
Conclusions
This study highlights the exciting opportunity to use brain PET imaging to investigate metabolism during virtual exposure and reports the involvement of the visual-motor control system in the treatment of acrophobia by VRET.
https://ift.tt/2NTobC1
Εγγραφή σε:
Αναρτήσεις (Atom)
-
Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
-
Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
-
heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
